Excision of translesion synthesis errors orchestrates responses to helix-distorting DNA lesions

Tsaalbi-Shtylik, Anastasia; Ferrás, Cristina; Pauw, Bea; Hendriks, Giel; Temviriyanukul, Piya; Carlée, Leone; Calléja, Fabienne M.G.R.; Hees, Sandrine van; Akagi, Jun‐ichi; Iwai, Shigenori; Hanaoka, Fumio; Jansen, Jacob G.; Wind, Niels de

doi:10.1083/jcb.201408017

Cited by 17 publications

(18 citation statements)

References 62 publications

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“…In this pathway, MutSα targets mismatches formed by TLS opposite (6-4)PP lesions thereby acting downstream of NER and TLS [126]. The presence of long-lived excision intermediates consisting of gapped DNA coated with RPA serves as a signal for ATR kinase and will give rise to broken chromosomes upon replication in the next cell cycle.…”

Section: Oxidative Damage and Dna Adductsmentioning

confidence: 99%

“…In the case of Lynch syndrome colorectal cancer, the rate of cellular proliferation is surely an important contributor, but it is unlikely to be the only factor. Tsaalbi-Shtylik et al suggest that the loss of post-TLS repair and attendant elevated mutagenesis leads to disruption of multiple tumor suppressing functions, and in combination with constant exposure to intestinal genotoxins, may explain the colorectal tropism of Lynch syndrome [126]. …”

Section: Oxidative Damage and Dna Adductsmentioning

confidence: 99%

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DNA mismatch repair and the DNA damage response

2016

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This review discusses the role of DNA mismatch repair (MMR) in the DNA damage response (DDR) that triggers cell cycle arrest and, in some cases, apoptosis. Although the focus is on findings from mammalian cells, much has been learned from studies in other organisms including bacteria and yeast [1,2]. MMR promotes a DDR mediated by a key signaling kinase, ATM and Rad3-related (ATR), in response to various types of DNA damage including some encountered in widely used chemotherapy regimes. An introduction to the DDR mediated by ATR reveals its immense complexity and highlights the many biological and mechanistic questions that remain. Recent findings and future directions are highlighted.

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Section: Oxidative Damage and Dna Adductsmentioning

confidence: 99%

Section: Oxidative Damage and Dna Adductsmentioning

confidence: 99%

DNA mismatch repair and the DNA damage response

2016

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“…Consistent with their role in surveying the replication products of Pol IV, the ϵ exonuclease and Pol II affect several Pol IV-dependent mutagenic phenomena ( 9 , 56 ). In addition, it has been demonstrated that the eukaryotic heterodimer Msh2/Msh6 suppress UV-induced mutagenesis by mediating the excision of incorrect nucleotides introduced by error-prone TLS Pols ( 57 ).…”

Section: Discussionmentioning

confidence: 99%

MutS regulates access of the error-prone DNA polymerase Pol IV to replication sites: a novel mechanism for maintaining replication fidelity

Fernández

Malchiodi

et al. 2016

Nucleic Acids Res

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Translesion DNA polymerases (Pol) function in the bypass of template lesions to relieve stalled replication forks but also display potentially deleterious mutagenic phenotypes that contribute to antibiotic resistance in bacteria and lead to human disease. Effective activity of these enzymes requires association with ring-shaped processivity factors, which dictate their access to sites of DNA synthesis. Here, we show for the first time that the mismatch repair protein MutS plays a role in regulating access of the conserved Y-family Pol IV to replication sites. Our biochemical data reveals that MutS inhibits the interaction of Pol IV with the β clamp processivity factor by competing for binding to the ring. Moreover, the MutS–β clamp association is critical for controlling Pol IV mutagenic replication under normal growth conditions. Thus, our findings reveal important insights into a non-canonical function of MutS in the regulation of a replication activity.

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“…A recent study of ES cells derived from mice harboring defects in NER and/or MMR and exposed to short wavelength UVC irradiation suggests a novel "post-TLS" repair pathway in proliferating cells for MMR-dependent, UV-induced mutagenesis and DNA damage signaling. In this pathway, MutSα targets mismatches formed by TLS opposite (6-4)PP lesions thereby acting downstream of NER and TLS [126]. The presence of long-lived excision intermediates consisting of gapped DNA coated with RPA serves as a signal for ATR kinase and will give rise to broken chromosomes upon replication in the next cell cycle.…”

Section: Oxidative Damage and Dna Adductsmentioning

confidence: 99%

DNA Mismatch Repair and the DNA Damage Response

2013

Encyclopedia of Biological Chemistry

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Excision of translesion synthesis errors orchestrates responses to helix-distorting DNA lesions

Abstract: An Msh2/Msh6-dependent DNA repair mechanism mitigates the mutagenicity of photolesions and induces cell cycle responses by excising incorrect nucleotides incorporated by postreplicative translesion synthesis.

Cited by 17 publications

References 62 publications

DNA mismatch repair and the DNA damage response

DNA mismatch repair and the DNA damage response

MutS regulates access of the error-prone DNA polymerase Pol IV to replication sites: a novel mechanism for maintaining replication fidelity

DNA Mismatch Repair and the DNA Damage Response

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